What is the appropriate evaluation and management for an adult with nighttime pruritus?

Nighttime Pruritus: Evaluation and Management

Immediate First-Line Management

For nighttime itching in adults, start high-lipid emollients applied twice daily to the entire body plus a moderate-potency topical corticosteroid (hydrocortisone 2.5% or clobetasone butyrate) to affected areas 3-4 times daily for at least 2 weeks, combined with first-generation sedating antihistamines at bedtime (diphenhydramine 25-50 mg or hydroxyzine 25-50 mg) specifically for their sedative properties to address nighttime pruritus. 1, 2

Why This Approach Works

• Xerosis (dry skin) is the most common cause of pruritus in adults, particularly in elderly patients, and emollients address impaired barrier function that worsens at night 2, 3
• The 2-week trial with topical steroids excludes asteatotic eczema before pursuing systemic causes 2
• First-generation antihistamines are specifically recommended for nighttime pruritus due to their sedative properties, unlike non-sedating antihistamines which should be reserved for daytime use 1

Critical caveat: Avoid long-term use of sedating antihistamines in elderly patients (>65 years) due to increased fall risk and potential dementia association 2

Essential Diagnostic Workup

Order these baseline laboratory tests for any adult with persistent nighttime pruritus:

• Complete blood count with ferritin – Iron deficiency accounts for approximately 25% of generalized pruritus cases and symptoms resolve within days of iron repletion 4, 2
• Liver function panel including total bilirubin and serum bile acids – Cholestatic liver disease characteristically produces pruritus involving palms/soles that intensifies at night 4
• Renal function panel (urea, creatinine, electrolytes) – Uremic pruritus severity correlates with chronic kidney disease stage 4, 2

Additional tests are not routinely ordered but should be added based on specific clinical features 2:

• Thyroid function, fasting glucose, LDH, and ESR only when endocrine/metabolic disorders are suspected
• JAK2 V617F mutation if aquagenic pruritus (water-triggered itching) suggests polycythemia vera 1, 4
• Peripheral blood film if elevated hemoglobin/hematocrit raises concern for polycythemia vera 1, 2

Red-Flag History Features

These clinical patterns demand specific investigation:

• Palm and sole involvement with nocturnal worsening → strongly suggests cholestatic liver disease 4
• Aquagenic pruritus (itch triggered by water contact) → hallmark of polycythemia vera, order JAK2 mutation testing 1, 4
• Weight loss, fevers, night sweats, or lymphadenopathy → suspect lymphoma, refer for lymph node biopsy 1, 4
• Recent medication changes → drug-induced pruritus accounts for ~12.5% of cases and is reversible after withdrawal 4, 2

Cause-Specific Treatment Algorithms

Iron-Deficiency Pruritus

Oral iron supplementation leads to complete cessation of itching within days of therapy 4

Uremic Pruritus (Chronic Kidney Disease)

• First-line: Broadband UVB phototherapy (Level 1+ evidence) 4
• Second-line: Gabapentin 300 mg at bedtime, titrate to 900-1200 mg daily 4

Cholestatic Liver Disease

• First-line: Rifampin 150 mg twice daily 4
• Second-line: Cholestyramine 9 g daily if rifampin ineffective 4
• Refer to hepatology for significant hepatic impairment 4

Polycythemia Vera

• First-line: Aspirin 300 mg daily provides effective relief 1, 4
• Alternatives: Cytoreductive therapy, interferon-α, SSRIs, or UVB phototherapy 1, 4

Lymphoma-Associated Pruritus

• Urgent referral for lymph node excision or core biopsy 4
• Symptomatic options: Cimetidine, gabapentin, carbamazepine, mirtazapine, or phototherapy 1, 4
• High-dose oral corticosteroids provide palliative relief during definitive treatment 1

Second-Line Systemic Therapy (If Initial Management Fails After 2 Weeks)

For persistent nighttime pruritus despite emollients and topical steroids:

• Gabapentin 300 mg at bedtime, titrate to 900-3600 mg daily – specifically recommended for elderly pruritus and neuropathic itch 1, 4, 2
• Alternative: Pregabalin 25-150 mg daily 1, 4

Important warning: Avoid gabapentin in patients with hepatic disease as it can precipitate hepatic encephalopathy 4

Additional Management Strategies

For Refractory Cases (After 2-4 Weeks)

• Antidepressants: Paroxetine, fluvoxamine, or mirtazapine 4
• Opioid antagonists: Naltrexone or butorphanol 4
• Anti-emetics: Ondansetron or aprepitant 1, 4

Psychosocial Interventions

Chronic pruritus significantly reduces quality of life and causes sleep disturbances in up to one-third of patients 1, 5. Consider:

• Education on trigger avoidance and proper treatment application 1
• Relaxation techniques and cognitive restructuring 1
• Habit reversal training for scratching behavior 1
• Referral to liaison psychiatry or psychology for distressed patients 1

Common Pitfalls to Avoid

• Do not use crotamiton cream, topical capsaicin, or calamine lotion – these are ineffective for generalized pruritus 2
• Do not routinely screen for malignancy – investigations should be guided by history and physical examination, not ordered reflexively 2
• Do not use sedating antihistamines long-term in elderly patients – increased dementia risk and falls 2
• Do not overlook medication review – in patients ≥80 years, opioids (tramadol), SSRIs (sertraline), atypical antidepressants (trazodone, mirtazapine), and inhaled corticosteroids (budesonide) commonly cause pruritus 2

Referral Indications

• Dermatology: Pruritus persisting >2-4 weeks despite first-line therapy or unclear etiology 4
• Hepatology: Significant liver dysfunction or refractory cholestatic itch 4
• Hematology: Suspected polycythemia vera (elevated hemoglobin with positive JAK2 mutation) or lymphoma 4, 2
• Skin biopsy consideration: Persistent unexplained pruritus may rarely represent cutaneous lymphoma or small-fiber neuropathy 1, 4, 2

Follow-Up Protocol

Regular follow-up is essential because systemic causes may emerge over time, and treatment efficacy should be reassessed at each visit 4. Approximately 15-25% of chronic pruritus cases have an underlying systemic disease 4, with nocturnal worsening particularly pointing to cholestatic liver disease, uremia, or iron deficiency 4.